RESEARCH

Our laboratory focuses on understanding how cellular heterogeneity contributes to the pathogenesis of human liver 

diseases using cholangiocyte biology as a platform. Cholangiocytes (biliary cells) comprise a highly dynamic 

population of cells with morphologically and functionally distinct subtypes that arise from different developmental 

origins. Similarly, cholangiopathies refer to a diverse group of disorders that impair biliary cellular homeostasis with 

varying etiologies and pathology. Using a novel selective biliary injury model and integrated genetic and 

pharmacological approaches in complementary in vivo and in vitro systems, we are elucidating the pathogenesis of 

human biliary diseases with emphases on deciphering mechanisms conferring functional heterogeneity of 

cholangiocytes in injury responses and how disruption of these processes can drive a biliary phenotype. We also aim to deconstruct gene-environment interactions underlying biliary diseases with the ultimate goal of conceiving and testing novel therapeutic strategies.  

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       OUTBREAKS OF BILIARY ATRESIA

Biliary atresia is an extrahepatic neonatal cholangiopathy that is the most common cause of chronic liver disease in children. Epidemics of biliary atresia had occurred in newborn livestock in Australia in setting of maternal ingestion of the Dysphania plant species during pregnancy. 

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  IDENTIFICATION OF         BILIATRESONE

We used an in vivo biliary secretion assay in zebrafish larvae to isolate biliatresone, a previously unknown electrophilic isoflavone, from Dysphania that is responsible for the biliary atresia outbreaks in newborn livestock. 

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SELECTIVE TOXICITY   OF BILIATRESONE

Despite its reactive nature, biliatresone is selectively toxic to the extrahepatic biliary system in the zebrafish as evidenced by the selective destruction of the gallbladder (arrow).